Fewer and higher doses of radiation may be effective at treating patients with head and neck squamous cell carcinoma, according to new findings presented by Bentzen et al at the 2023 American Society for Radiation Oncology (ASTRO) Annual Meeting (Abstract LBA 02).
Background
Head and neck squamous cell carcinoma—the seventh most common type of cancer in the world—accounts for 450,000 deaths per year and is predominantly diagnosed in patients who reside in low- and middle-income countries. Historically, the disease has been associated with tobacco and alcohol use, including secondhand smoke and chewing tobacco. Although HPV-associated head and neck squamous cell carcinoma typically occurs in younger and healthier patients, cancers related to tobacco and alcohol generally affect older patients who have comorbidities that can complicate treatment.
“Head and neck cancer caused by factors other than the human papillomavirus (HPV) remains a significant burden, especially in lower- and middle-income countries,” explained lead study author Søren Bentzen, PhD, DMSc, Professor of Radiation Oncology and Director of the Division of Biostatistics and Bioinformatics in the Department of Epidemiology and Public Health at the University of Maryland School of Medicine. “This is a trial that directly informs how you can effectively deliver radiation therapy to patients in a resource-scarce environment,” he added.
Unlike in the United States and many other high-income countries, the incidence of head and neck squamous cell carcinoma is rising in low- and middle-income countries, where rates are already disproportionately high. For instance, head and neck cancer accounts for 30% of all cancer diagnoses in India compared with 4% to 5% globally, and an estimated 84% of deaths from the disease occur in low- and middle-income countries.
Standard treatment for patients with locally advanced head and neck squamous cell carcinoma in these countries typically involves up to 7 weeks of radiation therapy. Low- and middle-income countries often face a substantial scarcity of radiation therapy facilities, and patients who reside there may be forced to travel great distances and remain away from home for long periods of time to receive care.
Previous findings have indicated that shorter, more intense radiation courses could deliver outcomes similar to current treatment regimens.
Study Methods and Results
In the new phase III HYPNO clinical trial, researchers randomly assigned 792 patients with locally advanced head and neck squamous cell carcinoma across 10 low- and middle-income countries—Uruguay, Brazil, Argentina, Cuba, South Africa, India, Pakistan, Thailand, Indonesia, and the Philippines—to undergo either a hypofractionated regimen of 20 fractions (55 Gy, five fractions per week for 4 weeks) or a normofractionated regimen of 33 fractions (66 Gy, six fractions per week for 5.5 weeks). The researchers also assigned 73% of the patients to undergo chemotherapy.
A variety of tumor sites were represented, most commonly the oropharynx (50.5%). The patients were predominantly male (87%), and most of them had a history of smoking or chewing tobacco (87%). The majority of them were diagnosed with stage III or IV disease (73%), and nearly half of them had cancer that metastasized to their lymph nodes (49%).
After a follow-up of 3 years, the researchers found that the patients who received the accelerated hypofractionated treatment regimen had roughly the same level of locoregional tumor control (test for noninferiority within a 10% margin, P = .041) and late-term side effects (test for noninferiority within a 10% margin, P = .004) as those who received the longer normofractionated treatment regimen. Additionally, there were no statistically significant differences in the overall survival rates (P = .62, 54.1% hypofractionated vs 55.5% normofractionated) and progression-free survival rates (P = .42, 44.0% vs 45.3%, respectively) between the groups.
The researchers determined that delivering a course of radiation in 20 rather than 33 treatment sessions was comparable in efficacy at controlling cancer in those with alcohol- and tobacco-related disease—without increasing side effects.
Conclusions
“Accelerating radiation treatment is tricky, because delivering too high a dose or too many doses too quickly can cause side effects that lower a [patient’s] quality of life. But not delivering enough radiation may allow the cancer to return,” stressed Dr. Bentzen. “There is actually a sweet spot where you get exactly the right balance between the total dose, the total treatment time, and the dose you deliver in each fraction. The net result is that you hit the tumor hard enough to get good control, but you don’t affect the normal tissue more than you would with the standard treatment,” he underscored.
The researchers are currently completing additional subgroup analyses to validate the efficacy of the accelerated regimen in a wide variety of patient types.
Disclosure: For full disclosures of the study authors, visit astro.org.
